The Changing Prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) in Turkey in the Last Decade.

BACKGROUND/AIMS: The true prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) is unknown in Turkey due to a lack of population-based studies. The aim of this study was (i) to determine the overall and region-specific prevalence of NAFLD in Turkey; (ii) to analyze the factors associated with the prevalence; and (iii) to determine the nationwide change in the prevalence of NAFLD in the last decade. MATERIALS AND METHODS: The 10-year data (2007 to 2016) of 113,239 apparently healthy subjects visiting the check-up clinics of Acibadem Hospitals Group were retrospectively analyzed. A subgroup of patients (n=8120) statistically representing the bigger cohort were selected. The prevalence was analyzed according to ultrasound findings, age, sex, body mass index (BMI), geographical region, and time periods trisected as 2007-2010, 2011-2013 and 2014-2016. RESULTS: The overall prevalence of NAFLD in Turkey was found to be 48.3%. It was highest among people >50 years of age (65.6%), male sex (64.0%), with a BMI>25 kg/m2 (63.5%) and in Central and Eastern Anatolia regions (57.1% and 55.7%, respectively). The prevalence of NAFLD was 43.5% between 2007-2010, 47.6% between 2011-2013 and 53.1% between 2014-2016 and the rate of increase was 22%. Multivariate analysis showed that male sex, serum alanine aminotransferase (ALT) level, older age, BMI, type-II diabetes mellitus, hypertension and dyslipidemia were independent factors associated with NAFLD. CONCLUSION: NAFLD is a highly prevalent disease affecting almost half of the Turkish population (48.3%). We are faced with a dramatic increase in NAFLD prevalence in the past 10 years.

Determination of the upper limits of normal serum alanine aminotransferase (ALT) level in healthy Turkish population.

Background and Aim: Recent studies have reported that the widely accepted range of upper limits of normal (ULN) alanine aminotransferase (ALT) levels (ULN<40U/L) is high for the healthy population. We aimed to find the correct ULN level for men and women in a presumed healthy liver population group. Materials and Methods: The data of 7410 healthy subjects visiting the check-up clinics were retrospectively analysed in this study. Patients were divided in to "healthy liver group" (n=2694) and "high-risk liver group" (n=4716) based on fatty liver on ultrasound, existing of chronic liver disease, ongoing significant alcohol consumption, diabetes mellitus and dyslipidaemia. Receiver operating characteristic (ROC) curves were generated and the area under the curve (AUC) was calculated at the 95th percentiles for both men and women. Results: The AUC score of ALT for men was 0.92, and the ULN for the serum ALT in men was found as 32.10 U/L (sensitivity of 0.89, specificity 0.85). The AUC score of ALT for women was 0.90, and the ULN for serum ALT was found as 23.15 U/L (sensitivity of 0.90, the specificity of 0.88). Conclusion: ULN for serum ALT level should be lowered and different cut-off values should be used for men (32.10 U/L) and women (23.15 U/L).

Regular coffee intake improves liver enzyme levels and liver histology in patients with chronic alcohol consumption, non-alcoholic fatty liver and non-alcoholic steatohepatitis: Report of 259 cases.

Background and Aim: This study aims to investigate the effects of chronic coffee consumption (>5 years) and type of coffee in non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver (NAFLD) and patients who have regular alcohol consumption. Materials and Methods: In this study, 158 healthy individuals and 101 patients with histologically proven NASH were enrolled. The daily amount of coffee intake, amount of alcohol use and type of coffee were calculated for all patients. The degree of steatosis and fibrosis was analyzed by transient elastography and liver ultrasound in non-NASH and by liver biopsy in NASH patients. Results: Patients with a history of coffee consumption (n=132) had lower liver enzyme levels compared to the non-coffee group (n=127) (p=0.001). Serum ALT level was significantly lower [ALT: 21.2±11.7 U/L vs. 56.4±15.6 U/L (p=0.004)], and the liver histopathology was significantly better for patients with a coffee consumption of daily for >5years (p=0.045 for fibrosis score for NASH, p=0.036 for LSM and p=0.015 for CAP measurements for the non-NASH patient). Conclusion: Coffee seems to have a positive protective effect on liver histology and liver enzyme levels in healthy individuals, in patients with chronic alcohol consumption, NAFLD and NASH. These results are more prominent in patients who drink coffee on a regular daily base for more than five years.

Real-world efficacy and safety of Ledipasvir + Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience.

BACKGROUND/AIMS: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population. MATERIAL AND METHODS: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)±ribavirin (RBV) orombitasvir/paritaprevir/ritonavir±dasabuvir (PrOD)±RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed. RESULTS: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90±54.60 U/L to 17.00±14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51±4.54 to 7.32±3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0±16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%). CONCLUSION: LDV/SOF or PrOD±RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.

The relationship between heterotopic gastric mucosa in the cervical esophagus and laryngopharyngeal reflux.

OBJECTIVES: This study aims to investigate the possible correlations between the heterotopic gastric mucosa (HGM) islets in the cervical esophagus and laryngopharyngeal reflux (LPR). PATIENTS AND METHODS: Between May 2010 and April 2011, 45 patients (36 females, 9 males; mean age 39.8±14.1 years; range 18 to 72 years) who had reflux symptom index (RSI) >10 and reflux finding score (RFS) >7 were included. The study group consisted of 21 patients who were diagnosed with HGM islets in the cervical esophagus, while control group consisted of 24 patients without any HGM islets assessed by upper gastrointestinal system endoscopy. Esophagus manometric examination and dual-channel 24-hour pH monitoring were performed on all patients. RESULTS: Pretreatment mean RSI and RFS were 25.6±3.5 and 15.1±3.4 in group 1, while it was found to be 21.1±4.4 and 11.9±2.6 in group 2 (p=0.001, p=0.001). A total of 29.7% of patients who underwent pH monitoring had distal reflux, whereas 43.2% of them had proximal reflux. In group 1, distal reflux was observed in 15.4% and proximal reflux was found in 54% of the patients, while distal reflux was observed in 38% and proximal reflux was found in 38% of the patients in group 2 (p=0.152; p=0.27). Fourteen patients diagnosed with HGM had antral- and seven patients had fundal-type epithelium. CONCLUSION: Our study results suggest that HGM islets may be considered as an etiological factor in the patients with severe LPR with isolated proximal reflux based on the 24-hour pH monitoring.

The advantage of retrieval PEG tubes in patients with buried bumper syndrome - a case report.

The aging population has resulted in an increasing need for long-term enteral nutrition of patients with a wide range of disabling conditions. Percutaneous endoscopic gastrostomy is one of the applicable methods for long-term enteral nutrition support. The buried bumper syndrome is a rarely encountered but grave complication of percutaneous endoscopic gastrostomy. Various internal and external methods have been described for the removal of the buried bumper. Removing the percutaneous endoscopic gastrostomy tube by external traction without an abdominal incision can resolve this problem efficiently, especially in cases in whom retrieval-type percutaneous endoscopic gastrostomy tubes have been used. We report a case of buried bumper syndrome as a late complication of percutaneous endoscopic gastrostomy placement. We removed the buried bumper with external traction and placed a new percutaneous endoscopic gastrostomy tube in a different site because of the peristomal infection.

A Burkitt's Lymphoma Case Mimicking Crohn's Disease: A Case Report.

Lymphomas are solid tumors that arise from lymphoid tissue and present themselves as Hodgkin's or non-Hodgkin's lymphoma. Particularly gastrointestinal lymphomas can be clinically confused with other gastrointestinal tumors as well as with diffuse and inflammatory bowel disease. Early diagnosis and treatment bear vital importance in the management of lymphomas due to their high proliferation rates. In this report, we are presenting a case which initially displayed clinical and radiological signs of Crohn's disease, but was eventually diagnosed as Burkitt's lymphoma by laparotomy, and also we aim to underscore the importance of differential diagnosis.

Clinical outcomes of liver transplantation for HBV-related hepatocellular carcinoma: data from the NIH HBV OLT study.

BACKGROUND: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is an indication for orthotopic liver transplantation (OLT) in patients with tumor stage within the United Network for Organ Sharing criteria. The number of patients listed for HBV-related HCC is increasing, while the number of patients listed for HBV-related cirrhosis is declining presumptively because of the availability of more effective oral nucleos(t)ide analogues. This study presents the final, long-term outcome of patients transplanted for HBV-related HCC in the National Institutes of Health (NIH) HBV OLT Study Group. RESULTS: Ninety-eight patients (52.4%) in the NIH HBV OLT cohort underwent OLT for HBV-related HCC. With a mean follow-up of 36.5 months post-OLT, 12 (12.2%) patients developed recurrence of HCC. Multivariate analysis did not find a statistically significant role of gender, tumor stage at OLT, pre-OLT HCC treatment, recurrence of HBV, or duration of HCC diagnosis pre-OLT in predicting HCC recurrence. Serum alpha-fetoprotein (AFP) level >200 ng/mL at transplant was found to be statistically significant in predicting HCC recurrence (p=0.003). HCC recurrence was significantly associated with decreased post-OLT survival. CONCLUSION: HCC is the most common indication for OLT in patients with chronic hepatitis B in the era of more effective oral antivirals. Serum AFP at the time of OLT is significantly associated with HCC recurrence.

Liver transplantation outcomes among Caucasians, Asian Americans, and African Americans with hepatitis B.

Several previous studies found that Asians transplanted for hepatitis B virus (HBV) infection had worse post-transplant outcomes than Caucasians. Data on post-transplant outcomes of African Americans and waitlist outcomes of Asian Americans and African Americans with hepatitis B are scant. The aim of this study was to compare waitlist and post-transplant outcomes among Asian Americans, African Americans, and Caucasians who had HBV-related liver disease. Data from a retrospective-prospective study on liver transplantation for HBV infection were analyzed. A total of 274 patients (116 Caucasians, 135 Asians, and 23 African Americans) from 15 centers in the United States were enrolled. African Americans were younger and more Asian Americans had hepatocellular carcinoma (HCC) at the time of liver transplant listing. The probability of undergoing transplantation and the probability of survival on the waitlist were comparable in the 3 racial groups. Of the 170 patients transplanted, 19 died during a median follow-up of 31 months. The probability of post-transplant survival at 5 years was 94% for African Americans, 85% for Asian Americans, and 89% for Caucasians (P = 0.93). HCC recurrence was the only predictor of post-transplant survival, and recurrence rates were similar in the 3 racial groups. Caucasians had a higher rate of HBV recurrence: 4-year recurrence was 19% versus 7% and 6% for Asian Americans and African Americans, respectively (P = 0.043). In conclusion, we found similar waitlist and post-transplant outcomes among Caucasians, Asian Americans, and African Americans with hepatitis B. Our finding of a higher rate of HBV recurrence among Caucasians needs to be validated in other studies.

Cerebral sinus thrombosis in a patient with active ulcerative colitis and double heterozygosity for Factor V Leiden and prothrombin gene mutations.

Inflammatory bowel diseases are associated with increased risk for thrombotic complications, In patients with ulcerative colitis (UC) cerebral sinus venous thrombosis (CSVT) is an extremely rare complication. We report a patient with active UC and CSVT. The patient was heterozygous for Factor V Leiden and G20210A prothrombin gene mutations without other identifiable precipitating factors. This patient highlights the need for investigating the patients with UC with thrombotic complications for other thrombophilic states.

Update on viral hepatitis: 2008.

PURPOSE OF REVIEW: The present review is a concise review of recent developments in the field of viral hepatitis, based on publications between December 2007 and November 2008. RECENT FINDINGS: The incidence of acute hepatitis A and B infection has declined significantly, especially among children less than 15 years of age. Five oral antiviral agents have been approved for the treatment of chronic hepatitis B. Telbivudine is more potent than lamivudine but is associated with a high rate of antiviral resistance compared with entecavir or tenofovir. De-novo combination of lamivudine and adefovir reduces the rate of antiviral resistance compared with lamivudine monotherapy. Individualizing dose and duration of pegylated interferon and ribavirin according to on-treatment virologic response may improve sustained virologic response rates. Several specifically targeted antiviral therapies notably protease and polymerase inhibitors are promising but must be used in combination with pegylated interferon and ribavirin. Hepatitis E virus has been reported to result in chronic hepatitis in transplant patients. SUMMARY: Multiple treatment options are available for hepatitis B but long-term treatment is required. Several specifically targeted antiviral therapies have shown promise. In the meantime, individualizing dose and duration of pegylated interferon and ribavirin might improve sustained virologic response rates in patients with hepatitis C.

Indications for therapy in hepatitis B.

Increased treatment options that are more efficacious and safe and new knowledge on the natural history of chronic hepatitis B virus (HBV) infection have expanded the indications for therapy in hepatitis B. The question is no longer "Who should be treated?" but "When should treatment be initiated?" Treatment is clearly indicated in patients with life-threatening liver disease (acute liver failure, decompensated cirrhosis, or severe hepatitis flare) and in those with compensated cirrhosis and high levels of serum HBV DNA. For patients with precirrhotic liver disease, treatment indications should be based on clinical, biochemical, or histological evidence of liver disease, such as elevated alanine aminotransferase (ALT) levels, abnormal histology, and high levels of serum HBV DNA. The cutoff for ALT and HBV DNA values are constantly being revised and should be set at a lower level for older patients who may have been infected for a longer period of time. High serum HBV DNA levels persisting for a few decades are associated with increased risk of clinical outcomes, but there is insufficient data to support the initiation of treatment based on high serum HBV DNA alone, particularly in young patients, those with persistently normal ALT levels, and those with a single high HBV DNA level. The decision to initiate treatment at the time of assessment or to defer treatment should take into consideration other factors such as desire to start a family, occupational requirement, family history of hepatocellular carcinoma, access to care and insurance coverage, and commitment to long-term treatment and medication compliance. All patients who are not initiated on treatment should continue to be monitored so treatment can be started if and when the indication arises.

What is the optimal regimen for preventing hepatitis B recurrence after liver transplantation?

The outcome of liver transplantation for hepatitis B has markedly improved in the last two decades. This commentary discusses the findings and limitations of a study by Hwang et al., which retrospectively examined the outcome of 639 adult patients who underwent living donor liver transplantation for hepatitis B. The authors reported a 5-year HBV recurrence rate of 7.3% and concluded that high-dose hepatitis B immunoglobulin (HBIG) monotherapy and rescue antiviral therapy is an effective way to prevent HBV recurrence after liver transplantation. With the availability of safe and effective antiviral agents associated with low rates of drug resistance, HBIG monotherapy is rarely used. The standard approach involves administration of antiviral therapy to suppress HBV replication before transplantation, followed by a combination of HBIG and antiviral therapy after transplantation. Combination prophylaxis permits the dose of HBIG to be reduced, which results in cost savings and reduces rates of HBV recurrence.

Sensitivity and accuracy of an updated line probe assay (HBV DR v.3) in detecting mutations associated with hepatitis B antiviral resistance.

BACKGROUND/AIMS: Early detection of antiviral drug-resistant mutations enables prompt initiation of rescue therapy. The aim of this study was to determine the accuracy and sensitivity of a new line probe assay in the detection of antiviral drug-resistant HBV mutations. METHODS: One-hundred samples from 54 patients with virologic breakthrough during entecavir, lamivudine or adefovir treatment and 21 samples from 21 nucleoside-naïve patients were tested by direct sequencing and an updated line probe assay (Innogenetics, HBV DR v.3) which incorporates probes that can detect mutations at 11 positions of the reverse transcriptase region of the HBV polymerase gene. RESULTS: Complete concordance between line probe and sequencing results was observed for 90/121 samples (74.3%) and 1291/1331 amino acid positions (96.9%). Testing of follow-up samples and clonal analysis of discordant samples confirmed the presence of mutations where line probe assay but not direct sequencing detected mutations. HBV DR v.3 assay consistently detected mutations present in > or = 5% of the virus population when HBV DNA concentration was > or = 4 log10copies/mL. CONCLUSIONS: The updated version of the line probe assay (HBV DR v.3) has high concordance with direct sequencing in detecting antiviral drug-resistant mutations but its sensitivity in detecting mutations at some positions needs to be improved.

Impact of the hepatitis B virus genotype on pre- and post-liver transplantation outcomes.

Emerging data suggest that the hepatitis B virus (HBV) genotype and the precore and core promoter variants impact the outcome of orthotopic liver transplantation (OLT) for hepatitis B. The aim of this study was to determine if there is a correlation between HBV genotype, precore and core promoter variants, and pre- and post-OLT outcomes. Serum samples from patients participating in the National Institutes of Health HBV-OLT study were tested for HBV genotype and precore and core promoter variants. A total of 123 patients were studied: 43% were Asians, 46% were Caucasians, and 8% were African Americans. HBV genotypes A (35%) and C (35%) were the most prevalent, followed by genotypes D and B. Precore and core promoter variants were detectable in 44% and 90% of patients. Patients with genotype C were more likely to have hepatocellular carcinoma (HCC) at listing (P < 0.001). Waitlist mortality was highest among patients with genotype D, while posttransplant mortality was highest among patients with genotype C. Precore or core promoter variants did not correlate with pre- or post-OLT survival. In conclusion, in this US patient population, patients with genotype C were more likely to have HCC at the time of transplant listing and to die after transplant than patients with non-C genotypes. Patients with genotype D had the highest posttransplant survival, but this was offset by higher waitlist mortality. Our study suggests that HBV genotypes but not precore or core promoter variants may have an impact on pre- and post-OLT outcomes of hepatitis B patients.